FIV infection has the potential to be a very useful model of human immunodeficiency virus (HIV) infection in humans, but that potential has not been realized because of the slow development of disease in infected cats (years to develop immunosuppression) with the current limited number of cloned infectious strains of FIV. The PI has isolated, cloned, and characterized a strain of FIV, FIV-Oma, from a non-domestic cat (Pallas cat) that replicates in a broader range of cell types than domestic cat FIV strains, grows to higher titer and causes more extensive and varied cytopathic effects (CPE). Unfortunately, this clone replicates variably in domestic cats. The main thrust of this application is to engineer a variety of chimeric clones by exchanging critical regions of FIV-Oma with FIV-PPR, a clone of domestic cat FIV. The resultant chimeras will be tested for host cell range, replicative ability, and cytotoxic and fusogenic effects in a variety of cell lines and primary cell cultures. Constructs with the enhanced biological properties of FIV-Oma will be introduced into domestic cats to assess their ability to replicate and cause disease in vivo.